The exquisite discriminatory capacity and sensitivity of the mammalian olfactory system is thought to result from a series of complex signal transduction mechanisms that reside within the primary sensory neuron. Odorous molecules are detected by olfactory receptors linked to G-proteins, intracellular second messengers, and ion channels, generating neuronal signals that are conveyed to the brain where this information is processed and perceived as odor. Preliminary studies revealed a subset of olfactory sensory neurons that utilize a cGMP-mediated signaling system and project axons to specific glomeruli in the olfactory bulb, some of which have been implicated as part of a pathway processing odor cues for suckling behavior in neonatal rats. The long-term goal is to understand the diversity of olfactory sensory neurons, identify their signal transduction systems and decipher the neural pathways to, and within, the brain that allow perception of specific odors and control of innate behavior. The hypothesis to be tested contends that a specific subset of olfactory neurons, and the glomeruli to which they project, perform a unique biological function in the mammalian olfactory system. This is mediated by a membrane guanylyl cyclase possibly functioning as an olfactory receptor, coupling cGMP synthesis with changes in neuronal excitability. To test this hypothesis, a multidiscipline approach will characterize the biochemical features of the pathway, including odorant-response characteristics, and the influence of genetic manipulation of pathway components on animal behavior. Double labeling immunofluorescence techniques and single cell reverse transcriptase polymerase chain reactions will allow the identification of molecular components of the signaling systems involved. The biological or chemical signals, eliciting a response in guanylyl cyclase-expressing neurons will be determined, and the contribution of guanylyl cyclase to olfactory signaling and regulation of innate behavior will be evaluated by characterizing the phenotype of mice lacking guanylyl cyclase. This research offers the potential for resolving definitively a role of the cGMP signaling system in olfactory function such as the suckling response of neonates. It is expected to provide further insight into the fundamental mechanisms underlying the transduction, encoding and processing of information in the mammalian chemosensory system. This knowledge will find general application for understanding signaling systems in the brain.